crossing96/oncoscreening huggingface dataset:
Variation in Statewide Intravesical Treatment Rates for Non-Muscle Invasive Bladder Cancer During the Bacillus Calmette-Guerin Drug Shortage.	OBJECTIVE: To measure the changes in treatment patterns for non-muscle invasive bladder cancer before and during the Bacillus Calmette-Guerin (BCG) drug shortage. MATERIALS AND METHODS: We used a 5% random sample of Medicare beneficiaries and identified 7971 bladder cancer patients (2648 pre-BCG shortage and 5323 during the shortage) ≥66 years of age who received intravesical treatment within 1 year of diagnosis between 2010 and 2017. The BCG shortage period was defined from July 2012 ongoing. Full induction treatment with BCG, mitomycin C, gemcitabine, or other intravesical agents was defined as receiving ≥5 of 6 treatments within 60 days. State-level BCG use before and during the drug shortage was compared in US states reporting at least 50 patients in each period. Independent variables included year of index date, age, sex, race, rurality, and region of residence. RESULTS: BCG utilization rates decreased 5.9% in the shortage period (95% CI (-8.2%)-(-3.7%)). The proportion of patients that completed a full induction course of BCG decreased from 31.0% in the pre-shortage period to 27.6% in the shortage period (P = .002). 84% of reporting states (16 of 19) had decreased BCG utilization ranging between 5% and 36% compared to pre-shortage rates. CONCLUSION: During the BCG drug shortage, eligible bladder cancer patients were less likely to receive gold standard intravesical BCG with a large variation in treatment patterns between US states.	bladder
Latency period of aristolochic acid-induced upper urinary tract urothelial carcinoma.	PURPOSE: Aristolochic acid (AA) is a carcinogen in upper urinary tract urothelial carcinoma (UTUC). This study investigated the latency period between AA exposure and UTUC development. MATERIALS AND METHODS: This population-based cohort study was designed using record linkage of the National Health Insurance Research Database (NHIRD), Taiwan Cancer Registry Dataset, and cause-of-death data in Taiwan. Those aged 40-79 years were enrolled in this study. Patients who died or had renal insufficiency or UTUC before 2005 were excluded. The doses of AA exposure and rates of comorbidities between 2000 and 2005 were obtained. The Cox proportion hazard model was used to estimate the risk of UTUC between 2005 and 2016. In addition, the Cox model with time-varying coefficient of AA was used to measure the latency period of UTUC. RESULTS: Of the 752,232 participants enrolled from the NHIRD, 520,871 (68.29%), 210,447 (27.59%), and 31,415 (4.12%) were exposed to cumulative AA doses of 0-1 mg, 1-150 mg, and >150 mg, respectively. A total of 1,147 (0.15%) patients were diagnosed with UTUC between 2005 and 2016. The latency periods of UTUC in middle-aged (40-59 years old) men with cumulative AA doses of 1-150 mg and middle-aged women with cumulative AA doses of 1-150 mg and >150 mg were 8, 9, and 7 years, respectively. Among the aged (60-79 years) individuals, no time-varying effect was observed, and the latency period could not be measured. CONCLUSION: A decreased risk of UTUC was observed after the ban on AA in Taiwan, especially in middle-aged women with moderate to high doses of AA exposure and men with moderate doses of AA exposure. The latency period of UTUC varies with age, the dose of AA exposure, and sex.	bladder
Evidence for virus-mediated oncogenesis in bladder cancers arising in solid organ transplant recipients.	A small percentage of bladder cancers in the general population have been found to harbor DNA viruses. In contrast, up to 25% of tumors of solid organ transplant recipients, who are at an increased risk of developing bladder cancer and have an overall poorer outcomes, harbor BK polyomavirus (BKPyV). To better understand the biology of the tumors and the mechanisms of carcinogenesis from potential oncoviruses, we performed whole genome and transcriptome sequencing on bladder cancer specimens from 43 transplant patients. Nearly half of the tumors from this patient population contained viral sequences. The most common were from BKPyV (N=9, 21%), JC polyomavirus (N=7, 16%), carcinogenic human papillomaviruses (N=3, 7%), and torque teno viruses (N=5, 12%). Immunohistochemistry revealed variable Large T antigen expression in BKPyV-positive tumors ranging from 100% positive staining of tumor tissue to less than 1%. In most cases of BKPyV-positive tumors, the viral genome appeared to be clonally integrated into the host chromosome consistent with microhomology-mediated end joining and coincided with focal amplifications of the tumor genome similar to other virus-mediated cancers. Significant changes in host gene expression consistent with the functions of BKPyV Large T antigen were also observed in these tumors. Lastly, we identified four mutation signatures in our cases, with those attributable to APOBEC3 and SBS5 being the most abundant. Mutation signatures associated with an antiviral drug, ganciclovir, and aristolochic acid, a nephrotoxic compound found in some herbal medicines, were also observed. The results suggest multiple pathways to carcinogenesis in solid organ transplant recipients with a large fraction being virus-associated.	bladder
Intravesical oncolytic virotherapy and immunotherapy for non-muscle-invasive bladder cancer mouse model.	OBJECTIVES: To test if intravesical instillation of both an anti-programmed cell death protein 1 (PD-1) inhibitor and an oncolytic reovirus would demonstrate a greater effect than either treatment alone, as non-muscle-invasive bladder cancer that is refractory to intravesical bacillus Calmette-Guérin can be treated by systemic anti-PD-1 immunotherapy and we previously demonstrated improved overall survival (OS) with six once-weekly instillations of intravesical anti-PD-1 in a murine model. MATERIALS AND METHODS: Using an orthotopic syngeneic C3H murine model of MBT2 urothelial bladder cancer, groups of 10 mice were compared between no treatment, intravesical anti-PD-1, intravesical oncolytic reovirus, or intravesical reovirus + anti-PD-1. A single intravesical treatment session was given. The primary outcome was OS, and the secondary outcomes included long-term immunity and tumour-immune profile. RESULTS: With a median follow-up of 9 months, all mice that received no treatment died with a median survival of 41 days, while the comparison median OS was not reached for reovirus (hazard ratio [HR] 14.4, 95% confidence interval [CI] 3.9-32.6; P < 0.001), anti-PD-1 (HR 28.4, 95% CI 7.0-115.9; P < 0.001), and reovirus + anti-PD-1 (HR 28.4, 95% CI 7.0-115.9; P < 0.001). Monotherapy with anti-PD-1 or reovirus demonstrated no significant differences in survival (P = 0.067). Mass cytometry showed that reovirus + anti-PD-1 treatment enriched monocytes and decreased myeloid-derived suppressor cells, generating an immuno-responsive tumour microenvironment. Depletion of CD8(+) T cells eliminated the survival advantage provided by the intravesical treatment. CONCLUSIONS: Treatment of murine orthotopic bladder tumours with a single instillation of intravesical reovirus, anti-PD-1 antibody, or the combination confers superior survival compared to controls. Tumour-immune microenvironment differences indicated myeloid-derived suppressor cells and CD8(+) T cells mediate the treatment response.	bladder
Voiding and renal function 10 years after radical cystectomy and orthotopic neobladder in women.	OBJECTIVES: To assess long-term voiding and renal function (RF) changes after radical cystectomy (RC) and orthotopic neobladder (ONB) surgery in women without disease recurrence. MATERIAL AND METHODS: Women who underwent RC and ONB reconstruction between 1995 and 2011 were included in this study. Patients who developed disease failure or were lost to follow-up were excluded. The study outcomes were long-term voiding function and the incidence and predictors of RF deterioration (defined as >20% decline of baseline). Analysis was performed using the log-rank test and Cox regression analysis. RESULTS: The study included 195 patients with a median (interquartile range) follow-up of 98 (53-151) months, of whom 95 had >10 years of follow-up. Daytime continence, night-time continence and chronic urine retention (CUR) were identified in 170 (87%), 134 (69%) and 52 patients (27%), respectively. Among patients with >10 years of follow-up, 82 (86%), 66 (70%) and 31 (33%) had daytime continence, night-time continence and CUR at the last follow-up visit, respectively. RF deterioration events occurred in 74 patients throughout the follow-up and chronic kidney disease (CKD) stage III-V developed in 80 patients. Patients' age (hazard ratio [HR] 1.41, 95% confidence interval [CI]1.06-1.89; P = 0.02) and serous-lined extramural tunnel diversion (HR 0.43, 95% CI 0.19-0.86; P = 0.02) were the independent predictors of RF deterioration. Among patients with >10 years of follow-up, RF deteriorated in 46 patients (49%) and CKD stage III-V developed in 40 (42%). CONCLUSION: Women surviving more than 10 years after RC and ONB maintained acceptable continence status, apart from having a higher CUR rate, compared to those followed for <10 years. However, RF deterioration developed in nearly half of them.	bladder
India Ink Tattooing of Ureteroenteric Anastomoses.	While upper tract access through the insensate conduit following urinary diversion takes less time and incurs fewer costs than percutaneous kidney access does for the treatment of ureter and kidney pathology, endoscopic ureteroenteric anastomoses (UEA) identification can be difficult. We injected India Ink into the bowel mucosa near the UEA during ileal conduit diversion (IC) to determine the safety and feasibility of ink tattooing. Patients undergoing IC were prospectively randomized to receive ink or normal saline (NS) injections. The injections were placed 1 cm from UEA in a triangular configuration, and loopogram exams and looposcopy were performed to identify reflux (UR), UEA, the tattooing site and strictures in 10 and 11 patients randomized with respect to ink and NS injections, respectively. Ink patients were older (72 vs. 61 years old, p = 0.04) and had a higher Charlson Comorbidity Index (5 vs. 2, p = 0.01). Looposcopy was performed in three ink and four NS patients. Visualization of UEA was achieved in 100% of the ink and 75% of the NS patients (p = 0.26). The ink ureteroenteric anastomotic stricture (UEAS) rate was higher (N = 3 vs. N = 1) and six patients vs. one patients underwent surgery, respectively, for UEAS (p = 0.31). The study was halted early due to safety concerns. Our pilot study demonstrates that ink can be well visualized following injection near UEA during IC. However, the ink cohort had more UEAS than previously cited in the literature and our prior institutional UEAS rate of 6%. While this study sample is small, the higher incidence of UEAS after ink injection led us to question the utility and safety of ink injection following IC.	bladder
The combination of oxaliplatin and anti-PD-1 inhibitor promotes immune cells infiltration and enhances anti-tumor effect of PD-1 blockade in bladder cancer.	INTRODUCTION: Bladder cancer (BLCA) is a highly malignant tumor of the urinary system, but the prognosis and survival rates have little improvement based on current therapeutic strategy. Immune checkpoint inhibitors (ICIs) therapy revolutionized the treatment of BLCA, but the clinical application of ICIs is limited by low response rate. Oxaliplatin (OXP), a second line chemotherapy drug for BLCA, may reshape the tumor immune microenvironment (TIME) via recruiting immune cells. Here, we conducted the study of oxaliplatin combined with anti-PD-1 inhibitor in BLCA mice models. METHODS: The 6-8 weeks old female C57BL/6J mice were used to establish subcutaneous model of bladder tumor. After tumors developed, mice were given tail vein injections of PBS or oxaliplatin (2.5 mg/kg) and/or anti-PD-1 antibody (10 mg/kg). Tumor tissue samples and peripheral blood mononuclear cell (PBMC) were collected to systemically evaluate the efficiency and safety of combination OXP and anti-PD-1 inhibitor. The change of immune cells populations and the corresponding phenotypic diversity in TIME and PBMC were analysed by flow cytometry. RESULTS: Tumor growth experiments clarified that the combination therapy was more efficient than medication alone. Flow cytometry analysis of tumor samples showed significant differences between untreated and treated mice. Oxaliplatin influences the TIME by increasing immune cells infiltration, including CD3(+) T cells, CD4(+) T cells, CD8(+) T cells, dendritic cells (DC cells) and natural killer cells (NK cells). As for infiltrating cells, oxaliplatin upregulated the expression of CD134 and downregulated TIM-3 of CD4(+) T cells, downregulated the PD-L1 expression of DC cells, which contributed to improve the anti-tumor effect and the treatment response of ICIs. Additionally, the evaluation of PBMC found that there were no significant changes in immune cell subsets and phenotypes, which validated the safety of the combination therapy. These results show the therapeutic potential for the combination of OXP and anti-PD-1 inhibitor in BLCA. CONCLUSION: OXP could increase the infiltration of immune cells in TIME to promote the anti-tumor activity of anti-PD-1 inhibitor. The present research provided an appropriate rationale of combination chemotherapy and immunotherapy therapy for BLCA.	bladder
A case of rare metachronous four primary carcinoma.	PURPOSE: When more than two tumors are diagnosed in the same person, it is called multiple primary cancer. It is rare to be diagnosed as four primary cancers. Here, we present one elderly male patient suffered from testicular seminoma, gastric cancer, bladder cancer and breast cancer from 1946 to 2019. METHODS: When he was about 1.5 years old in 1946, his mother (a doctor) inadvertently found that the left scrotum of the child was enlarged. He performed left testicular resection under general anesthesia and postoperative pathological report: left testicular seminoma. In March 2007 (62 years old), the upper abdomen was distended and uncomfortable after eating, accompanied by hiccups and heartburn. He performed distal subtotal gastrectomy and postoperative pathology report: moderately and poorly differentiated adenocarcinoma of ulcer. In May 2013 (68 years old), he developed no obvious cause of painless gross hematuria. He performed robot-assisted laparoscopic radical cystectomy+pelvic lymph node dissection+bilateral ureterostomy and postoperative pathological report: invasive high-grade urothelial carcinoma at the bottom of the bladder. In February 2017 (72 years old), he found the right breast was developing, and a nodule was palpable under the skin. He performed undergo modified radical surgery in the right breast and postoperative pathological report: Invasive breast cancer. RESULTS: During the past 70 years, he suffered from four types of tumors, all of which underwent surgical treatment. Postoperative pathology confirmed that they were malignant tumors. Genetic tumor gene testing found no pathogenic or suspected pathogenic mutations. The patient's general condition is good, with regular follow-up and no tumor recurrence CONCLUSION: The treatment of multiple primary cancers is different from tumor recurrence. Targeted treatment for different tumors can achieve good therapeutic results. Cancer patients must be followed up regularly. Timely treatment after discovering new tumors is the key to a good prognosis.	bladder
Effectiveness and safety of immune checkpoint inhibitor monotherapy in advanced upper tract urothelial carcinoma: A multicenter, retrospective, real-world study.	INTRODUCTION: The effectiveness and safety of immune checkpoint inhibitor (ICI) monotherapy in advanced upper tract urothelial carcinoma (UTUC) is less reported. METHODS: In total, 106 consecutive advanced UTUC patients receiving ICI monotherapy were collected from nine high volume centers. Clinical outcomes were analyzed according to multiple parameters (e.g., treatment line, metastatic sites). Objective response rate (ORR), overall survival (OS) and progression-free survival (PFS) were captured after ICI initiation. RESULTS: With a median follow-up of 12.0 months, 25 patients in the first-line group and 15 patients in the second-line group died of UTUC. We reported a median OS of 18.0 months, a median PFS of 5.0 months, and an ORR of 38.6% for patients in the first-line group; a median OS of 10.0 months, a median OS of 4.0 months, and an ORR of 27.8% for patients in the second-line group. Complete response was observed in two patients in the first-line group and one patient in the second-line group with a total complete response rate of 2.8%. In the univariate and multivariate analysis, visceral metastasis with a hazard ratio of 2.4 was associate with poor OS. The most common treatment-related adverse events included fatigue (11.3%), pruritus (10.4%), and diarrhea (6.6%). CONCLUSIONS: This real-world study suggests that ICI monotherapy is active and has acceptable toxic effects for unresectable or metastatic UTUC as first-line therapy in cisplatin-ineligible patients or second-line therapy in platinum-refractory patients.	bladder
Adjuvant intravesical treatment in patients with intermediate and high-risk non-muscle-invasive bladder cancer with BCG versus MMC applied with COMBAT or EMDA. Results of a prospective study.	BACKGROUND: Bacillus Calmette-Guerin (BCG) maintenance therapy is the standard adjuvant treatment of high- and intermediate-risk non-muscle-invasive bladder cancer (NMIBC). However, the problems of shortages and the adverse effects, both local and systemic, that it causes lead to the search for alternatives with devices that improve the penetration of intravesical chemotherapeutics. MATERIALS AND METHODS: Prospective observational study was conducted from August 2018 to August 2022. Patients diagnosed with intermediate and high-risk NMIBC without CIS who received one of the following three treatments were included: BCG in induction protocol with six weekly instillations and maintenance with three weekly instillations at months 3, 6, and 12. MMC was applied by Physionizer(®) 30 device with a current of 20 mA for 30 min was used in an induction protocol of 6 weekly instillations followed by 6 monthly instillations as maintenance (EMDA group). MMC was applied by COMBAT BRS System V2.0 device at 43 ± 0.5 ℃ for 60 min was used in an induction protocol of 6 weekly instillations followed by 6 monthly instillations as maintenance (HIVEC group). The primary objective was to compare the 24-month recurrence-free rate between the three groups. The secondary objectives were to evaluate the rate free of progression at 24 months and the degree of toxicity of the treatments. RESULTS: One hundred and eighty-three patients divided into a HIVEC group with sixty-one patients, EMDA group with fifty-nine patients, and BCG group with sixty-three patients. After a mean follow-up of 25 months (IQR 13-36), the 24-month recurrence-free rate was 82.1% for HIVEC, 80% for EMDA, and 84.6% for BCG (p > 0.05), and a progression-free rate at 24 months of 95.6% for HIVEC, 98.3% for EMDA, and 92.9% for BCG (p > 0.05). No statistically significant differences were found between the three groups with respect to the degree of reported adverse events. CONCLUSION: Adjuvant treatment with BCG or MMC applied with COMBAT or EMDA does not present differences in the recurrence-free rate and progression at 24 months in our population of patients with intermediate- and high-risk NMBC without CIS.	bladder
Role of PD-1/PD-L1-mediated tumour immune escape mechanism and microsatellite instability in the BCG failure of high-grade urothelial carcinomas.	"BACKGROUND: Intravesical BCG treatment fails inexplicably in 30%-45% of patients for high-grade nonmuscle-invasive bladder cancer (NMIBC). We aimed to investigate the role of PD-1/PD-L1 interaction on BCG failure of high-grade NMIBC and to identify biomarkers for predicting BCG responsive cases. METHODS: Thirty BCG responsive and 29 nonresponsive NMIBCs were included in the study. Expressions of PDL1(SP-263), MSH2, MSH6, PMS2, and MLH1 were evaluated on pre- and post-BCG transurethral resection (TUR-B) specimens by immunohistochemistry. PD-L1(SP-263) expression was categorised as negative/low, high. DNA mismatch repair protein (MMR) expressions were classified as ""reduced"" if ≤30% of nuclei stained, ""preserved"" if >30% of nuclei stained. Microsatellite instability (MSI) testing was performed by PCR using five mononucleotide markers. RESULTS: Reduced DNA MMR protein expression was found to be significantly higher in the pretreatment biopsies of BCG-responsive group than the BCG nonresponsive tumour group (p = 0.022). PD-L1 expression did not show any significant difference between the pre- and posttreatment TUR-B specimens of the BCG nonresponsive tumour group or between the pretreatment TUR-B specimens of BCG nonresponsive and the BCG responsive groups (p = 0.508, p = 0.708, respectively). DISCUSSION: Immune escape of tumour cells by PD-1/PD-L1 interaction does not seem to have any role in BCG failure of NMIBCs. Reduced MMR expression may help to determine cases that will respond well to BCG therapy. A better antitumour activity of BCG in NMIBCs with reduced MMR expression may be related to the ongoing accumulation of cancer neoantigens in correlation with increased tumour mutation load as a result of DNA repair defects."	bladder
Epigenomic mapping identifies an enhancer repertoire that regulates cell identity in bladder cancer through distinct transcription factor networks.	Muscle-invasive bladder cancer (BLCA) is an aggressive disease. Consensus BLCA transcriptomic subtypes have been proposed, with two major Luminal and Basal subgroups, presenting distinct molecular and clinical characteristics. However, how these distinct subtypes are regulated remains unclear. We hypothesized that epigenetic activation of distinct super-enhancers could drive the transcriptional programs of BLCA subtypes. Through integrated RNA-sequencing and epigenomic profiling of histone marks in primary tumours, cancer cell lines, and normal human urothelia, we established the first integrated epigenetic map of BLCA and demonstrated the link between subtype and epigenetic control. We identified the repertoire of activated super-enhancers and highlighted Basal, Luminal and Normal-associated SEs. We revealed super-enhancer-regulated networks of candidate master transcription factors for Luminal and Basal subgroups including FOXA1 and ZBED2, respectively. FOXA1 CRISPR-Cas9 mutation triggered a shift from Luminal to Basal phenotype, confirming its role in Luminal identity regulation and induced ZBED2 overexpression. In parallel, we showed that both FOXA1 and ZBED2 play concordant roles in preventing inflammatory response in cancer cells through STAT2 inhibition. Our study furthers the understanding of epigenetic regulation of muscle-invasive BLCA and identifies a co-regulated network of super-enhancers and associated transcription factors providing potential targets for the treatment of this aggressive disease.	bladder